The Search for Better Endometriosis Diagnosis

Author: Dora Koller, PhD, Principal Investigator at Women and Perinatal Health research group at Institut de Recerca Sant Pau, Yale School of Medicine | Editors: Romina Garcia de leon, Tashi Staamp 

Published: January 23, 2026

 

What is endometriosis? Recently, people have been comparing it to cancer as lesions can damage nearby tissue – is this accurate?

Endometriosis, a chronic systemic inflammatory disease, occurs when tissue similar to the endometrium (importantly, similar but not identical) grows outside the uterus. Several theories aim to explain its origin, including benign metastasis, vascular dissemination, and impaired cell death, which are also factors in cancer development and progression. In our recent study, the largest genomic study of endometriosis to date (preprint), we found molecular evidence for several of these processes, including these cancer-related mechanisms, hormonal imbalance, dysregulated immune response, and inflammation. Our findings, along with results from other researchers, suggest that the complex pathophysiology of endometriosis likely results from the interplay of multiple biological mechanisms rather than a single causal pathway, with considerable variation among women due to both genetic and environmental risk factors.

 

Many are told they “probably” have endometriosis but are deterred by invasive surgeries to diagnose. Is there research on how many people are living with undiagnosed endometriosis? 

Yes, research suggests that many people are living with undiagnosed endometriosis. A landmark study found that approximately 11% of women in the general population have undiagnosed endometriosis when screened with MRI. This is separate from and in addition to the 10% diagnosed prevalence, suggesting the total prevalence could be around 21%, meaning approximately 1 in 5 women may have some form of the disease.

 

There are recent biotech companies  and research groups looking at using blood tests to diagnose endometriosis. Are there any promising leads?

Yes, there are several promising leads. Ziwig developed the first non-invasive saliva test for endometriosis, now integrated into the French healthcare system, though experts have raised concerns about methodological issues and real-world performance. Blood tests are being developed by Kephera Diagnostics, Proteomics International, DotLab, and Endodiag. Based on published research, single biomarkers are not sufficient, and we need to analyze several biomarkers and the relationships between them. Menstrual fluid diagnostics are gaining significant traction, with multiple NIH RadXTech Act Endo Challenge finalists pursuing this approach: Endometrics aims to detect biomarkers from at-home collection kits, while Feinstein Institutes uses a new collection device designed for easier use, particularly for adolescents. Another company, Endogene.bio, is also developing menstrual fluid-based tests.

However, critical challenges remain: diagnosis alone is not enough, tests must be affordable, coupled to expert care, and able to distinguish between endometriosis and conditions like adenomyosis. There is also concern about inappropriate use as screening tools, which could lead to overdiagnosis, overtreatment, or false reassurance which delays necessary care for normalized pelvic pain. Pelvic pain should always be considered seriously regardless of test results.

 

In addition to blood tests, are there any new ‘non invasive’ surgery options for diagnosis?

Yes, there are companies working on more efficient MRI and ultrasound systems to help diagnose endometriosis. For example, EndoCure is developing AI-powered robotic ultrasound for endometriosis detection. Other innovative approaches include 3CPM Company measuring altered gastrointestinal smooth muscle electrical activity caused by endometriosis-related neurotransmitters, and Washington University using wearable sensors to detect abnormal uterine contraction patterns even before visible lesions appear.

Also, several experts are emerging who can now successfully diagnose endometriosis using advanced ultrasound and MRI techniques. Expert-performed transvaginal ultrasound and MRI have become increasingly accurate for detecting deep infiltrating endometriosis and ovarian endometriomas, with sensitivity and specificity approaching 80-90% in experienced hands. This expertise-driven approach is reflected in the updated ESHRE guidelines, which now recommend that laparoscopy be reserved only for patients with negative imaging results and where empirical treatment is unsuccessful or not appropriate, rather than as a first-line diagnostic tool.

 

What are treatment options for endometriosis?

Apart from surgery in some cases, hormonal therapies are the first-line medical treatment, working by reducing estrogen levels to suppress lesion growth and inflammation. Options include combined oral contraceptives, progestins, GnRH agonists/antagonists that create a temporary menopausal state, and aromatase inhibitors. These require long-term use and often provide only temporary symptom relief, with a wide variety of possible side effects ranging from headaches and mood changes to bone density loss. Pain management with NSAIDs can provide symptomatic relief but doesn’t address underlying disease.

The major challenge is that most women try multiple medications sequentially with no way to predict which will work or cause side effects, a process that can take years. This is changing with our research: we just started recruiting patients for the first-ever endometriosis study using pharmacogenetic markers to predict drug response and side effects, led by Hospital Clínic de Barcelona and funded by La Marató Foundation. This precision medicine approach analyzes genetic variants affecting drug metabolism with the aim to help clinicians select appropriate treatments upfront, potentially eliminating the trial-and-error approach.

 

Is there anything else we should know about endometriosis? 

Endometriosis is a chronic systemic disease,  meaning it is not solely a gynecological condition, it affects the whole body and impacts both physical and mental health . Symptoms vary considerably between patients and even within the same patient over time, and risk factors appear to differ among individuals. Therefore, we need precision medicine approaches to diagnose, treat, and manage it effectively, moving away from the one-size-fits-all model toward personalized care that accounts for individual disease presentation, genetic profiles, and treatment response predictions.